p53 gene status and expression of p53, mdm2, and p21Waf1/Cip1 proteins in colorectal cancer

Abrogation of the normal p53 pathway is the most common molecular alteratio n in human cancer, p53 Gene status can be potentially assessed through the expression of proteins known to be activated by the wild-type p53 (wt p53) system, such as mdm2 and p21Waf1/Cip1. In this study, the frequency of mdm2 , p21Waf1/Cip1, and p53 protein expression was investigated using immunohis tochemistry (IHC) in 88 colorectal carcinomas (CRCs). The relationship betw een these expressions and p53 status was examined. p53 status and the immun ophenotypes characterizing these tumors were correlated with standard progn ostic variables. Mutation of p53 was detected using single-strand conformat ional polymorphism (SSCP) analysis and sequencing. Concordance between p53 gene status and p53 immunoreactivity was seen in 62 of 88 (70.45%) carcinom as. Mdm2 expression was found in 22 of 45 (48.88%) and 5 of 43 (11.62%) of the tumors with wt p53 and mutated p53 (P<0.0001), respectively. Predominan tly, higher p21Waf1/Cip1 expression was associated with wt p53 (P<0.001). A ll wt p53 cases that expressed mdm2 also expressed p21Waf1/Cip1. These resu lts suggest that there is a subgroup of CRCs in which p53 is functionally a ctive, inducing transcription of mdm2 and Waf1/Cip2. Their combined evaluat ion may provide important clues for planning adjuvant systemic therapy and gene therapy based on the restitution of p53 function. However, no signific ant association was found between the immunophenotypes and the standard pro gnostic variables investigated.